IL-33 is associated with alveolar dysfunction in patients with viral lower respiratory tract disease
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
Interleukin (IL)-33 is released following tissue damage, causing airway inflammation and remodelling via reduced IL-33 (IL-33red)/serum stimulation-2 (ST2) and oxidised IL-33 (IL-33ox)/receptor for advanced glycation end products (RAGE)/epidermal growth factor receptor (EGFR) pathways. This study aimed to identify associations of IL-33 with clinical outcomes and pathological mechanisms during viral lower respiratory tract disease (LRTD). Ultra-sensitive immunoassays were developed to measure IL-33red, IL-33ox and IL-33/sST2 complexes in samples from patients hospitalised with COVID-19. Immunohistochemistry and multiomics were used to characterise lung samples. Elevated IL-33 in the airway and IL-33/sST2 complex in the circulation correlated with poor clinical outcomes (death, need for intensive care or mechanical ventilation). IL-33 was localised to airway epithelial and endothelial barriers, whereas IL1RL1 was expressed on aerocytes, alveolar endothelial cells specialised for gaseous exchange. IL-33 increased expression of mediators of neutrophilic inflammation, immune cell infiltration, interferon signalling and coagulation in endothelial cell cultures. Endothelial IL-33 signatures were strongly related with signatures associated with viral LRTD. Increased IL-33 release following respiratory viral infections is associated with poor clinical outcomes and might contribute to alveolar dysfunction. Although this does not show a causal relationship with disease, these results provide a rationale to evaluate pathological roles for IL-33 in viral LRTD.
Date Issued
2025-04-01
Date Acceptance
2024-12-05
Citation
Mucosal Immunology, 2025, 18 (2), pp.312-325
ISSN
1933-0219
Publisher
Elsevier BV
Start Page
312
End Page
325
Journal / Book Title
Mucosal Immunology
Volume
18
Issue
2
Copyright Statement
© 2025 AstraZeneca UK LTD. Published by Elsevier Inc. on behalf of Society for Mucosal Immunology. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39662674
PII: S1933-0219(24)00124-7
Subjects
Aerocyte
Alarmin
Alveolar
COVID-19
IL-33
Viral LRTD
Publication Status
Published
Coverage Spatial
United States
Date Publish Online
2024-12-09